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Three-year corneal graft survival rate in high-risk cases treated with subconjunctival and topical bevacizumab.

Significance Statement


The risk of corneal graft rejection increases with the number of vascularized corneal quadrants in high risk cases such as vascularised leucoma, corneal combustion, ulcer,  graft rejection or Stevens-Johnson syndrome (SJS). Success rate in those eyes extends only from 20-40% as compared to low risk cases where over 90% of grafts remain clear. Vascular endothelial growth factor (VEGF) plays a crucial role in vascularized and inflamed recipient bed. Bevacizumab, a humanised monoclonal antibody that binds  and blocks isoforms of VEGF-A has already been safely applied in other pathological conditions in ophthalmology. Keeping in mind its ability to prevent neovascularisations in other eye segments, we tested both subconjunctival and topical bevacizumab potency to increase graft survival in high-risk eyes over a longer postoperative period of 3 years. The results of our study on fifty high-risk cases suggest that bevacizumab treatment can increase overall graft success rate by preventing neovascularisation, and consequently the immune reaction toward foreign tissue. The bevacizumab supplement to conventional post penetrating keratoplasty (PK) therapy in high risk cases has so far shown good results with no side effects and could be implemented in future treatment thus reducing the risk of graft failure and rejection. However, further prospective clinical trials are required to precisely determine the optimal dose, administration, frequency and eventual side effects of this novel treatment.

Figure legend: Patient with vascularized scar who has undergone penetrating keratoplasty and topical bevacizumab  treatment before (A) and 3 years postoperatively (B) with clear graft and vision 1.0.


Three-year corneal graft survival rate in high-risk cases treated with subconjunctival and topical bevacizumab. Global Medical Discovery






Journal Reference

Dekaris I, Gabrić N, Drača N, Pauk-Gulić M, Miličić N. Graefes Arch Clin Exp Ophthalmol. 2015 Feb;253(2):287-94.

Special Eye Hospital ‘Svjetlost’, Department of Ophthalmology, University of Rijeka, Heinzelova 39, 10000, Zagreb, Croatia, [email protected]



To evaluate the effect of combined subconjunctival and topical  bevacizumab  treatment on corneal graft  survival rate in high-risk eyes.


Prospective, consecutive, interventional case series. Fifty eyes of 50 high-risk patients scheduled for penetrating keratoplasty (PK) were included in the study; two Stevens-Johnson syndromes (SJS), five corneal combustions due to chemical burn, seven post-traumatic vascularised leucomas, 11 post-infectious vascularised leucomas, 19 rejected grafts and six corneal ulcers. Additional surgeries such as autologous limbal stem cell and/or amniotic membrane transplantation were performed together with PK in ten cases. All eyes received subconjunctival injection of 0.5 ml bevacizumab (25 mg/ml) after PK. Eyes with more than two quadrants of neovascularisation (NV) received bevacizumab drops (25 mg/ml) postoperatively for up to 12 weeks. Donor grafts were followed up for best-corrected visual acuity, graft clarity, change in NV, endothelial cell density loss (ECD), and adverse events. Mean follow-up was 36.5 months (range 32-61).


Best-corrected visual acuity increase was statistically significant in 82 % (41/50) of eyes 3 years after PK (paired t-test, p = 0.02). Thirty-five (70 %) high-risk grafts remained clear throughout the 3-year follow-up period. Decrease of corneal NV was observed in 84 % (42/50) of eyes treated with bevacizumab. ECD changed from preoperative 2,864 ± 301 down to 1,905 ± 187 cells/mm(2) at 3 postoperative years. A non-healing epithelial defect was recorded in one patient with SJS after 12 weeks of topical bevacizumab.


Combined subconjunctival and topical bevacizumab treatment may improve corneal graft survival rate in the majority of high-risk cases.

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